US5189016A - Nutrient compositions containing peptides and method for administering the same - Google Patents

Nutrient compositions containing peptides and method for administering the same Download PDF

Info

Publication number
US5189016A
US5189016A US07/525,861 US52586190A US5189016A US 5189016 A US5189016 A US 5189016A US 52586190 A US52586190 A US 52586190A US 5189016 A US5189016 A US 5189016A
Authority
US
United States
Prior art keywords
grams
glycine
administering
dipeptide
glutamine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
US07/525,861
Inventor
David C. Madsen
W. Bruce Rowe
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Baxter International Inc
Original Assignee
Clintec Nutrition Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Clintec Nutrition Co filed Critical Clintec Nutrition Co
Priority to US07/525,861 priority Critical patent/US5189016A/en
Assigned to CLINTEC NUTRITION CO., DEERFIELD, IL, A CORP. OF IL reassignment CLINTEC NUTRITION CO., DEERFIELD, IL, A CORP. OF IL ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: MADSEN, DAVID C., ROWE, W. BRUCE
Priority to EP91107924A priority patent/EP0457314A1/en
Application granted granted Critical
Publication of US5189016A publication Critical patent/US5189016A/en
Assigned to BAXTER INTERNATIONAL INC. reassignment BAXTER INTERNATIONAL INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CLINTEC NUTRITION COMPANY
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06104—Dipeptides with the first amino acid being acidic
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/18—Peptides; Protein hydrolysates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic

Definitions

  • This invention relates to nutrient compositions for use in clinical nutrition and more particularly, to nutrient compositions containing certain dipeptides.
  • Proteins are converted to amino acids in the digestive system and the resulting amino acids are used by the body for growth and development. In certain medical situations a patient may be unable to receive proteins. In these situations patients have been given free amino acids. Free amino acids, however, are sometimes not tolerated well by patients and may cause diarrhea and dehydration.
  • Adibi I U.S. Pat. No. 4,340,592
  • Adibi I requires glycine to be the peptide in the N-terminal position because "glycine-terminated oligopeptides achieve a desirable intact transport of the oligopeptide into a cell.
  • the glycine grouping protects the oligopeptide from hydrolysis into amino acids by the peptidases on a cell membrane . . .
  • the glycine grouping is also lipophilic and the oligopeptide has an enhanced transport through the cell membrane . . .
  • the glycine terminated oligopeptides are particularly water-soluble which permits the use of such oligopeptides in high concentration.” Col. 2, 11. 35-55.
  • Adibi II discloses a nutritional composition containing at least one oligopeptide consisting of a dipeptide or a tripeptide wherein the N-terminal amino acid residue is glycine residue and at least one oligopeptide consisting of a dipeptide or a tripeptide wherein the N-terminal amino acid residue is selected from the class consisting of alanine, lysine and arginine.
  • the oligopeptide concentration is from 0.2 to 30 weight percent.
  • the preferred range is from 5 to 15 weight percent of the oligopeptide.
  • the total protein nutrients in the compositions are from 2 to 40 weight percent.
  • Adibi et al. conclude that glycine is generally superior to other amino acids as the N-terminal amino acid residue in a dipeptide because a greater fraction of such an intravenously administered dipeptide reaches the tissues.
  • S. Adibi et al. Influence of Molecular Structure on Half-life and Hydrolysis of Dipeptides in Plasma: Importance of Glycine as N-Terminal Amino Acid Residue, 35 Metabolism 850, 835 (1986).
  • Pfrimmer & Co Another group that is studying nutrient compositions including dipeptides is Pfrimmer & Co.
  • Two European patents, 0,087,751, hereinafter Pfrimmer I and 0,087,750 (Pfrimmer II) disclose water-soluble peptides.
  • Pfrimmer I discloses a method to parenterally administer low water-soluble amino acids.
  • Two amino acids, tyrosine and cystine, individually have low solubility in water. These amino acids, however, are clinically useful.
  • the disclosed infusion method involves bonding these difficultly soluble amino acids to the two amino groups of the amino acid lysine to produce a tripeptide.
  • Pfrimmer II discloses the infusion of glutamine as a derivative substituted by ⁇ -aminoacyl residues on the ⁇ amino group. That is, glutamine is in the "c-terminal" position, in that its alpha amino nitrogen becomes part of the peptide bond with the other amino acid.
  • the preferred dipeptide preparation disclosed in Pfrimmer II is alanyl-glutamine. The aminoacylation of glutamine is reported to achieve a stabilization of the terminal amide group.
  • the amino acid analyses have been completed on blood samples from six of the piglets in the experimental group and on blood samples from seven of the piglets in the control group.
  • the plasma amino acid data listed below indicate that administration of the glycylglutamine dipeptide increases the plasma glutamine concentrations in the piglets in the experimental group compared to the concentrations measured in plasma from the piglets in the control group.
  • a nutrient composition comprising an aqueous solution having at least one dipeptide with an N-terminal amino acid selected from the class consisting of glutamine, asparagine, tyrosine, tryptophan, and arginine is provided.
  • Glutamine 4.8 grams/100 mL 30° C.
  • asparagine 3.5 grams/100 mL at 28° C.
  • tyrosine 0.45 grams/100 mL 25° C.
  • tryptophan (11.4 grams/100 mL 25° C.
  • arginine (15.0 grams/100 mL, at 21° C.) are all less soluble in water than glycine (25 grams/100 mL, 25° C.).
  • the C-terminal amino acid is selected from the group consisting of alanine, glycine, tryptopan, arginine, proline and serine.
  • the nutritional solutions contain from about 0.1 to 25.0 percent by weight of oligopeptides, preferably about 0.5 to 5.0 percent by weight. (Arginine solubil: 15.0 grams/100 Ml at 21° C.)
  • peptides in a nutrient composition compared to the administration of equivalent amounts of the free amino acids, will cause a decrease in osmolarity of the solution, will facilitate the administration of amino acids having low water solubility, and will stabilize heat-unstable amino acids such as glutamine, asparagine and tryptophan.
  • the aqueous solution may be suitable for intravenous feeding or for intragastrointestional administration.
  • the aqueous solution itself may contain the other nutrient additives such as fats, glucose, mono- or oligo-saccharides, minerals, trace elements and/or vitamins.
  • Aqueous clinical nutrient compositions are prepared which include at least one dipeptide.
  • the dipeptide would be added to enteral or parenteral formulations of either complete or incomplete nutritional content.
  • Each dipeptide has an N-terminal amino acid selected from the group consisting of glutamine, asparagine, tyrosine, tryptophan and arginine.
  • the C-terminal amino acid of the dipeptide is selected from the group consisting of alanine, glycine, proline, tryptophan, arginine and serine.
  • the concentration of the dipeptide in the aqueous solution is from 0.1 to 25.0 percent by weight.
  • the selection of the particular dipeptide depends upon the requirements for essential and nonessential amino acids.
  • the clinical nutritional solution can contain dextrose, lipid emulsions, vitamins, minerals and trace elements.
  • Dipeptide additives such as single or multiple entities, as well as a total nutritional formulation which contains dipeptides as one component among many are contemplated by this invention.
  • Dipeptide can be added to enteral or parenteral formulations of either complete or incomplete nutritional content.
  • each of the dipeptides is present as shown in Table 1.
  • the structural formula of a glutaminyl-glycine dipeptide is as follows: ##STR1##
  • the glutamine unit: ##STR2## supplies the N-terminal group in the glutaminyl-glycine dipeptide described above.
  • tyrosine and arginine function as the N-terminal amino acid in the dipeptides.
  • the aqueous oligopeptide may be ingested orally along with other nutrients such as conventional foods of prepared vitamins, fats, glucose or other mono-saccharides, oligosaccharides, minerals and trace elements.
  • a supply of the oligopeptide solution may be merged through a Y-connection with a supply of glucose solution or other parenteral solutions.
  • the oligopeptide solutions may be mixed with glucose solutions and/or other parenteral solutions to create a mixture which may be administered parenterally.
  • oligopeptides rather than free amino acids allows administration of the same amount of amino acid residue in solutions which are less hypertonic and therefore can be introduced into peripheral veins, which is not considered to be a surgical procedure.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Mycology (AREA)
  • Nutrition Science (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The present invention relates to nutrient compositions containing dipeptides and methods for administering the same. In particular, according to the present invention, a nutrient composition comprising an aqueous solution having at least one dipeptide with an N-terminal amino acid selected from the class consisting of glutamine, asparagine, tyrosine, tryptophan, and aspargine is provided. Glutamine (4.8 grams/100 ml at 30° C.), asparagine (3.5 grams/100 mL at 28° C.), tyrosine (0.45 grams/100 mL at 25° C.) and tryptophan (11.4 grams/100 mL at 25° C.) and arginine (15.0 grams/100 mL at 21° C.) are all less soluble in water than glycine (25 grams/100 mL at 25° C.). The C-terminal amino acid is selected from the group consisting of alanine, glycine, tryptophan, arginine, proline and serine. The nutritional solutions contain from about 0.1 to 25.0 percent by weight of oligopeptides, preferably about 0.5 to 5.0 percent by weight.

Description

BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to nutrient compositions for use in clinical nutrition and more particularly, to nutrient compositions containing certain dipeptides.
2. Description of the Prior Art
Proteins are converted to amino acids in the digestive system and the resulting amino acids are used by the body for growth and development. In certain medical situations a patient may be unable to receive proteins. In these situations patients have been given free amino acids. Free amino acids, however, are sometimes not tolerated well by patients and may cause diarrhea and dehydration.
It has been observed that the body can more effectively absorb certain small molecules called dipeptides or tripeptides. In particular, it has been observed that peptides containing the amino acid residue glycine in the N-terminal position are readily assimilable. U.S. Pat. No. 4,340,592 (hereinafter Adibi I). Adibi I requires glycine to be the peptide in the N-terminal position because "glycine-terminated oligopeptides achieve a desirable intact transport of the oligopeptide into a cell. The glycine grouping protects the oligopeptide from hydrolysis into amino acids by the peptidases on a cell membrane . . . The glycine grouping is also lipophilic and the oligopeptide has an enhanced transport through the cell membrane . . . The glycine terminated oligopeptides are particularly water-soluble which permits the use of such oligopeptides in high concentration." Col. 2, 11. 35-55.
It was later found, however, that if glycine-terminated oligopeptides are the only peptide in the nutrient solution, excess glycine may develope.
European Patent Application No. 0,182,356 (hereinafter Adibi II) discloses a nutritional composition containing at least one oligopeptide consisting of a dipeptide or a tripeptide wherein the N-terminal amino acid residue is glycine residue and at least one oligopeptide consisting of a dipeptide or a tripeptide wherein the N-terminal amino acid residue is selected from the class consisting of alanine, lysine and arginine. The oligopeptide concentration is from 0.2 to 30 weight percent. For total parenteral nutrition, the preferred range is from 5 to 15 weight percent of the oligopeptide. The total protein nutrients in the compositions are from 2 to 40 weight percent. These prior teachings suggest the use of amino acids having high solubility in water, such as glycine (25.0 grams/100 ml 25° C.), as the N-terminal amino acid in the oligopeptide.
Adibi et al. conclude that glycine is generally superior to other amino acids as the N-terminal amino acid residue in a dipeptide because a greater fraction of such an intravenously administered dipeptide reaches the tissues. S. Adibi et al., Influence of Molecular Structure on Half-life and Hydrolysis of Dipeptides in Plasma: Importance of Glycine as N-Terminal Amino Acid Residue, 35 Metabolism 850, 835 (1986).
Another group that is studying nutrient compositions including dipeptides is Pfrimmer & Co. Two European patents, 0,087,751, hereinafter Pfrimmer I and 0,087,750 (Pfrimmer II) disclose water-soluble peptides. Pfrimmer I discloses a method to parenterally administer low water-soluble amino acids. Two amino acids, tyrosine and cystine, individually have low solubility in water. These amino acids, however, are clinically useful. The disclosed infusion method involves bonding these difficultly soluble amino acids to the two amino groups of the amino acid lysine to produce a tripeptide.
Pfrimmer II discloses the infusion of glutamine as a derivative substituted by α-aminoacyl residues on the α amino group. That is, glutamine is in the "c-terminal" position, in that its alpha amino nitrogen becomes part of the peptide bond with the other amino acid. The preferred dipeptide preparation disclosed in Pfrimmer II is alanyl-glutamine. The aminoacylation of glutamine is reported to achieve a stabilization of the terminal amide group.
Experiments involving the use of total parenteral nutrition containing glycyl-glutamine dipeptides, however, suggest the potential adverse effect of the TPN formulation containing glycyl-glutamine. In this experiment slightly preterm, colostrum-deprived piglets were maintained on total parenteral nutrition from birth to day 7 of life. All piglets in this study have been enrolled and completed the study period in the University of Florida Piglet Neonatal Intensive Care Unit. Ten piglets in the control group received standard neonatal piglet total parenteral nutrition solution containing amino acids, glucose, lipid, vitamins and minerals. Eleven piglets in the experimental group received the same total perenteral nutrition formulation with the exception that 20% of the amino acids in the standard solution was replaced with glutamine. Since the glutamine was in the form of a dipeptide, administration of 1 gram of glutamine required the coadministration of approximately 0.5 gram of glycine. Nine piglets in each group completed the full 7 days of the study. One piglet in the control group and two piglets in the experimental group became septic. The two septic piglets in the experimental group exhibited signs of severe convulsions while the septic piglet in the control group exhibited no signs of convulsions.
To date, the amino acid analyses have been completed on blood samples from six of the piglets in the experimental group and on blood samples from seven of the piglets in the control group. The plasma amino acid data listed below indicate that administration of the glycylglutamine dipeptide increases the plasma glutamine concentrations in the piglets in the experimental group compared to the concentrations measured in plasma from the piglets in the control group.
______________________________________                                    
PLASMA GLUTAMINE CONCENTRATIONS                                           
CONTROL PIGLETS       EXPERIMENTAL PIGLETS                                
Piglet   nmol/ml      Piglet   nmol/ml                                    
______________________________________                                    
P253     215          P260     709                                        
P259     189          P263     805                                        
P262     358          P266     646                                        
P265     384          P269     415                                        
P268     255          P272     272                                        
P271     240          P275     417                                        
P274     266          MEAN:    544                                        
MEAN:    272                                                              
______________________________________
Based on the problems associated with the above discussed peptides, an alternate method to deliver low water-soluble, and potentially toxic amino acids, such as glutamine, is needed.
SUMMARY OF THE INVENTION
According to the present invention, a nutrient composition comprising an aqueous solution having at least one dipeptide with an N-terminal amino acid selected from the class consisting of glutamine, asparagine, tyrosine, tryptophan, and arginine is provided. Glutamine (4.8 grams/100 mL 30° C.), asparagine (3.5 grams/100 mL at 28° C.), tyrosine (0.45 grams/100 mL 25° C.) and tryptophan (11.4 grams/100 mL 25° C.) and arginine (15.0 grams/100 mL, at 21° C.) are all less soluble in water than glycine (25 grams/100 mL, 25° C.). The C-terminal amino acid is selected from the group consisting of alanine, glycine, tryptopan, arginine, proline and serine. The nutritional solutions contain from about 0.1 to 25.0 percent by weight of oligopeptides, preferably about 0.5 to 5.0 percent by weight. (Arginine solubil: 15.0 grams/100 Ml at 21° C.)
These peptides in a nutrient composition, compared to the administration of equivalent amounts of the free amino acids, will cause a decrease in osmolarity of the solution, will facilitate the administration of amino acids having low water solubility, and will stabilize heat-unstable amino acids such as glutamine, asparagine and tryptophan. The aqueous solution may be suitable for intravenous feeding or for intragastrointestional administration. The aqueous solution itself may contain the other nutrient additives such as fats, glucose, mono- or oligo-saccharides, minerals, trace elements and/or vitamins.
It is an object of this invention to provide a dipeptide having a low water-soluble amino acid in the N-terminal position of the dipeptide, i.e., its carboxyl group partakes in a peptide bond. It is a further object of this invention to provide a dipeptide having stability to sterilization, long-term stability and bioavailability.
DETAILED DESCRIPTION OF THE INVENTION
Aqueous clinical nutrient compositions are prepared which include at least one dipeptide. The dipeptide would be added to enteral or parenteral formulations of either complete or incomplete nutritional content. Each dipeptide has an N-terminal amino acid selected from the group consisting of glutamine, asparagine, tyrosine, tryptophan and arginine. The C-terminal amino acid of the dipeptide is selected from the group consisting of alanine, glycine, proline, tryptophan, arginine and serine.
The concentration of the dipeptide in the aqueous solution is from 0.1 to 25.0 percent by weight. The selection of the particular dipeptide depends upon the requirements for essential and nonessential amino acids. In addition to dipeptides the clinical nutritional solution can contain dextrose, lipid emulsions, vitamins, minerals and trace elements.
Dipeptide additives such as single or multiple entities, as well as a total nutritional formulation which contains dipeptides as one component among many are contemplated by this invention. Dipeptide can be added to enteral or parenteral formulations of either complete or incomplete nutritional content.
In a one liter of amino solution which contains 100 grams of amino acids plus dipeptides, each of the dipeptides is present as shown in Table 1.
              TABLE 1                                                     
______________________________________                                    
One Liter Solution                                                        
Dipeptide          Grams                                                  
______________________________________                                    
glutaminyl-glycine 0.1-25.0  grams                                        
glutaminyl-alanine 0.1-25.0  grams                                        
glutaminyl-arginine                                                       
                   0.1-25.0  grams                                        
gluatminyl-proline 0.1-25.0  grams                                        
Tyrosyl-glycine    0.1-8.0   grams                                        
Tyrosyl-alanine    0.1-8.0   grams                                        
Tyrosyl-proline    0.1-8.0   grams                                        
arginyl-tyrosine   0.1-8.0   grams                                        
______________________________________
The structural formula of a glutaminyl-glycine dipeptide is as follows: ##STR1## The glutamine unit: ##STR2## supplies the N-terminal group in the glutaminyl-glycine dipeptide described above. Similarly, tyrosine and arginine function as the N-terminal amino acid in the dipeptides.
METHOD OF ADMINISTRATION
The aqueous oligopeptide may be ingested orally along with other nutrients such as conventional foods of prepared vitamins, fats, glucose or other mono-saccharides, oligosaccharides, minerals and trace elements. For parenteral administration, a supply of the oligopeptide solution may be merged through a Y-connection with a supply of glucose solution or other parenteral solutions. The oligopeptide solutions may be mixed with glucose solutions and/or other parenteral solutions to create a mixture which may be administered parenterally.
The administration of oligopeptides rather than free amino acids allows administration of the same amount of amino acid residue in solutions which are less hypertonic and therefore can be introduced into peripheral veins, which is not considered to be a surgical procedure.
Although the invention has been shown in connection with certain specific embodiments, it will be readily apparent to those skilled in the art that various changes in form and arrangement of steps can be made to quit requirements without departing from the spirit and scope of the invention.

Claims (7)

We claim:
1. A nutrient composition comprising an aqueous solution including glutaminyl-glycine.
2. The nutrient composition of claim 1 further comprising another nutrient selected from the class consisting of lipid emulsion, glucose, oligosaccharides, minerals, trace elements and vitamins.
3. A nutrient composition comprising an aqueous solution of free amino acids and glutaminyl-glycine, said glutaminyl-glycine comprising from 0.1 to 25.0 percent by weight of said composition.
4. A method of administering a nutrient composition to a patient which comprises orally administering to said patient an aqueous solution of claim 1.
5. A method of administering a nutrient composition to a patient which comprises parenterally administering to said patient an aqueous solution of glutaminyl-glycine.
6. A method of administering a nutrient composition to a patient which comprises orally administering to said patient an aqueous solution of claim 3.
7. A method of administering a nutrient composition to a patient which comprises parenterally administering to said patient an aqueous solution including 0.1 to 25 percent by weight of glutaminyl-glycine.
US07/525,861 1990-05-18 1990-05-18 Nutrient compositions containing peptides and method for administering the same Expired - Fee Related US5189016A (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US07/525,861 US5189016A (en) 1990-05-18 1990-05-18 Nutrient compositions containing peptides and method for administering the same
EP91107924A EP0457314A1 (en) 1990-05-18 1991-05-16 Nutrient compositions containing peptides

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US07/525,861 US5189016A (en) 1990-05-18 1990-05-18 Nutrient compositions containing peptides and method for administering the same

Publications (1)

Publication Number Publication Date
US5189016A true US5189016A (en) 1993-02-23

Family

ID=24094899

Family Applications (1)

Application Number Title Priority Date Filing Date
US07/525,861 Expired - Fee Related US5189016A (en) 1990-05-18 1990-05-18 Nutrient compositions containing peptides and method for administering the same

Country Status (2)

Country Link
US (1) US5189016A (en)
EP (1) EP0457314A1 (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0646375A1 (en) 1993-10-05 1995-04-05 Clintec Nutrition Company Method of regulating blood amino acid levels
US5821217A (en) * 1995-10-27 1998-10-13 Beth Israel Deaconess Medical Center, Inc. Enteral formulation: low in fat and containing protein hydrolysates
US6649746B1 (en) 1999-05-07 2003-11-18 University Of Virginia Patent Foundation Biological production of stable glutamine, poly-glutamine derivatives in transgenic organisms and their use for therapeutic purposes
US20040097426A1 (en) * 1999-08-13 2004-05-20 Josef Neu Dipeptides for prevention of muscle breakdown and microbial infection
US6743945B1 (en) * 1998-06-01 2004-06-01 Fuji Oil Co., Ltd. Carboxylic acid and amino acid or amino condensate reactants and manufacturing method therefor
US20050070484A1 (en) * 2003-09-26 2005-03-31 Josef Neu Arginyl-glutamine dipeptide for treatment of pathological vascular proliferation
US20060229256A1 (en) * 2003-09-26 2006-10-12 Bristol-Myers Squibb Company Enternal administration of arginine and glutamine for abnormal vascular proliferation
US20090270337A1 (en) * 2008-04-29 2009-10-29 Conopco, Inc., D/B/A Unilever Composition Comprising Carbohydrates and Peptides which Comprise Tryptophan

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL9300356A (en) * 1993-02-25 1994-09-16 Stichting Instituut Veevoeding Method of increasing the production of economically useful animals, method for preparing a dry composition to be fed to economically useful animals, and the use of glutamine or an analogue thereof
DE4316326C1 (en) * 1993-05-15 1994-06-09 Fresenius Ag High calorie, low osmolarity intravenous nutrient soln. - contains aminoacid(s), carbohydrate(s), fat and electrolytes, is glycerol free and has neutral pH
WO1997000889A1 (en) * 1995-06-21 1997-01-09 Asahi Kasei Kogyo Kabushiki Kaisha Peptides binding to low-density lipoproteins
AU2011203039B2 (en) * 2004-02-23 2013-02-21 Trustees Of Tufts College Inhibitors of dipeptidylpeptidase IV for regulating glucose metabolism
BRPI0507972A (en) * 2004-02-23 2007-07-24 Tufts College compound, pharmaceutical composition, use of a compound, method for inhibiting the proteolytic activity of a postproline cleavage enzyme and packaged pharmaceutical composition
CA2697951A1 (en) * 2007-08-30 2009-03-05 University Of Waterloo Amino acid pairing-based self assembling peptides and methods
KR101080271B1 (en) * 2009-03-31 2011-11-08 주식회사 웰스킨 Ultraviolet-induced reaction controlling cosmetic composition containing dipeptide
BR112014001404A2 (en) * 2011-07-22 2017-03-01 Fresenius Kabi Deutschland Gmbh parenteral nutrition product for obese intensive care patients

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4340592A (en) * 1980-03-14 1982-07-20 Adibi Siamak A Nutrient compositions and method of administering the same
DE3206784A1 (en) * 1982-02-25 1983-09-01 Pfrimmer & Co Pharmazeutische Werke Erlangen Gmbh, 8520 Erlangen AMINO ACID PREPARATIONS CONTAINING GLUTAMINE
DE3206810A1 (en) * 1982-02-25 1983-09-01 Pfrimmer & Co Pharmazeutische Werke Erlangen Gmbh, 8520 Erlangen WATER-SOLUBLE PEPTIDES VERY SLIGHTLY SOLUBLE AMINO ACIDS
EP0182356A2 (en) * 1984-11-19 1986-05-28 The Montefiore Hospital Association of Western Pennsylvania Nutrient compositions
US4636490A (en) * 1983-04-20 1987-01-13 Sanofi Novel peptidic derivatives inhibiting gastric secretion, process for preparing them and drugs containing them
US4758675A (en) * 1986-07-14 1988-07-19 G. D. Searle & Co. 3-thiophene-substituted tyrosyl dipeptide amides
EP0346501A1 (en) * 1987-12-30 1989-12-20 Vsesojuzny Kardiologichesky Nauchny Tsentr Akademii Meditsinskikh Nauk Sssr Pharmaceutical preparation for treating immunodeficiency conditions
EP0347890A1 (en) * 1988-06-22 1989-12-27 Roussel Morishita Co., Ltd. Amino acid nutrient compositions
US4987123A (en) * 1988-02-24 1991-01-22 Ajinomoto Co., Inc. Compositions useful for the treatment and/or prevention of hepatic disorders, and their pharmaceutical use

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5102871A (en) * 1989-04-24 1992-04-07 Kyowa Hakko Kogyo Co., Ltd. Nutrient composition

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4340592A (en) * 1980-03-14 1982-07-20 Adibi Siamak A Nutrient compositions and method of administering the same
DE3206784A1 (en) * 1982-02-25 1983-09-01 Pfrimmer & Co Pharmazeutische Werke Erlangen Gmbh, 8520 Erlangen AMINO ACID PREPARATIONS CONTAINING GLUTAMINE
DE3206810A1 (en) * 1982-02-25 1983-09-01 Pfrimmer & Co Pharmazeutische Werke Erlangen Gmbh, 8520 Erlangen WATER-SOLUBLE PEPTIDES VERY SLIGHTLY SOLUBLE AMINO ACIDS
EP0087751A2 (en) * 1982-02-25 1983-09-07 PFRIMMER KABI GMBH & CO. KG Water-soluble peptides from very poorly soluble amino acids
EP0087750A2 (en) * 1982-02-25 1983-09-07 Kabi Pharmacia GmbH Amino acid preparations containing glutaminic residues
US4636490A (en) * 1983-04-20 1987-01-13 Sanofi Novel peptidic derivatives inhibiting gastric secretion, process for preparing them and drugs containing them
EP0182356A2 (en) * 1984-11-19 1986-05-28 The Montefiore Hospital Association of Western Pennsylvania Nutrient compositions
US4758675A (en) * 1986-07-14 1988-07-19 G. D. Searle & Co. 3-thiophene-substituted tyrosyl dipeptide amides
EP0346501A1 (en) * 1987-12-30 1989-12-20 Vsesojuzny Kardiologichesky Nauchny Tsentr Akademii Meditsinskikh Nauk Sssr Pharmaceutical preparation for treating immunodeficiency conditions
US4987123A (en) * 1988-02-24 1991-01-22 Ajinomoto Co., Inc. Compositions useful for the treatment and/or prevention of hepatic disorders, and their pharmaceutical use
EP0347890A1 (en) * 1988-06-22 1989-12-27 Roussel Morishita Co., Ltd. Amino acid nutrient compositions

Non-Patent Citations (72)

* Cited by examiner, † Cited by third party
Title
Abel et al, Improved Survival from Acute Renal Failure After Treatment With Intravenous Essential L Amino Acids and Glucose. The New England Journal of Medicine, vol. 288, No. 14, Apr. 5, 1973, 695 699. *
Abel et al, Improved Survival from Acute Renal Failure After Treatment With Intravenous Essential L-Amino Acids and Glucose. The New England Journal of Medicine, vol. 288, No. 14, Apr. 5, 1973, 695-699.
Adibi et al, Influence of Molecular Structure on Half Life and Hydrolysis of Dipeptides in Plasma: Importance of Glycine as N Terminal Amino Acid Residue, Metabolism, Col. 35, No. 9 (1986), 830 836. *
Adibi et al, Influence of Molecular Structure on Half-Life and Hydrolysis of Dipeptides in Plasma: Importance of Glycine as N-Terminal Amino Acid Residue, Metabolism, Col. 35, No. 9 (1986), 830-836.
Adibi, Intravenous Use of Glutamine in Peptide Form: Clinical Applications of Old and New Observations, Metabolism, vol. 38, No. 8 (1989), pp. 89 92. *
Adibi, Intravenous Use of Glutamine in Peptide Form: Clinical Applications of Old and New Observations, Metabolism, vol. 38, No. 8 (1989), pp. 89-92.
Adibi, Siamak A., "Experimental Basis for Use of Peptides as Substrates for Parenteral Nutrition: A Review", Meta. vol. 36, No. 10, 1987 pp. 1001-1011.
Adibi, Siamak A., Experimental Basis for Use of Peptides as Substrates for Parenteral Nutrition: A Review , Meta. vol. 36, No. 10, 1987 pp. 1001 1011. *
Albers, S. et al. "Availability of Amino Acids Supplied Intravenously in Healthy Man as Synthetic Dipeptides: Kinetic Evaluation of L-alanyl-L-glutamine and glycyl-L-tyrosine", 75 Clin. Sci. 463 (1988).
Albers, S. et al. Availability of Amino Acids Supplied Intravenously in Healthy Man as Synthetic Dipeptides: Kinetic Evaluation of L alanyl L glutamine and glycyl L tyrosine , 75 Clin. Sci. 463 (1988). *
Albers, S. et al., Availability of Amino Acids Supplied by Constant Intravenous Infusion of Synthetic Dipeptides in Healthy Man, Clin. 76 Sci. 643 (1989). *
Anderson et al, Effects of Excess Arginine with and Without Supplemental Lysine on Performance, Plasma Amino Acid Concentrations and Nitrogen Balance of Young Swine, Journal of Animal Science, vol. 58, No 2, 1984 369 377. *
Anderson et al, Effects of Excess Arginine with and Without Supplemental Lysine on Performance, Plasma Amino Acid Concentrations and Nitrogen Balance of Young Swine, Journal of Animal Science, vol. 58, No 2, 1984 369-377.
Anderson et al, Lysine and Arginine Requirements of the Domestic Cat, 1368 1372 (1979). *
Anderson et al, Lysine and Arginine Requirements of the Domestic Cat, 1368-1372 (1979).
Arginine as an Essential Amino Acid in Children With Argininosuccinase Deficiency, Nutrition Reviews, vol. 37, No. 4, 1979, 112 113. *
Arginine as an Essential Amino Acid in Children With Argininosuccinase Deficiency, Nutrition Reviews, vol. 37, No. 4, 1979, 112-113.
Auspen, 16th Annual Scientific Meeting, 18 19, Tyrosine Arginine (Tyr Arg): A Soluble Form of Tyrosine (1986). *
Auspen, 16th Annual Scientific Meeting, 18-19, Tyrosine-Arginine (Tyr-Arg): A Soluble Form of Tyrosine (1986).
Barbul et al, Arginine: Biochemistry, Physiology, and Therapeutic Implications, J. of Parenteral and Enteral Nutrition, vol. 10, No. 2, 1986, 227 238. *
Barbul et al, Arginine: Biochemistry, Physiology, and Therapeutic Implications, J. of Parenteral and Enteral Nutrition, vol. 10, No. 2, 1986, 227-238.
Barbul et al, Immunostimulatory Effects of Arginine in Normal and Injured Rats, Journal of Surgical Research 29, 228 235 (1980). *
Barbul et al, Immunostimulatory Effects of Arginine in Normal and Injured Rats, Journal of Surgical Research 29, 228-235 (1980).
Brandt, et al., "Parenteral Nitrition with an Amino Acid Solution Containing a Mixture of Dipeptides, Evidence for Efficient Utilization of Dipeptides in Man, " Contr. Infusion Ther. Clin. Nutr. 17, pp. 103-116 (1988).
Brandt, et al., Parenteral Nitrition with an Amino Acid Solution Containing a Mixture of Dipeptides, Evidence for Efficient Utilization of Dipeptides in Man, Contr. Infusion Ther. Clin. Nutr. 17, pp. 103 116 (1988). *
Brown et al, Transiently Reduced Activity of Carbamyl Phosphate Synthetase and Ornithine Transcarbamylase in Liver of Children with Reye s Syndrome, N. Engl J. Med, vol. 294, No. 16, 861 867, 1976. *
Brown et al, Transiently Reduced Activity of Carbamyl Phosphate Synthetase and Ornithine Transcarbamylase in Liver of Children with Reye's Syndrome, N. Engl J. Med, vol. 294, No. 16, 861-867, 1976.
Brusilow et al, Arginine Therapy of Argininosuccinase Deficiency, The Lancet, Jan. 29, 1979, 124 127. *
Brusilow et al, Arginine Therapy of Argininosuccinase Deficiency, The Lancet, Jan. 29, 1979, 124-127.
Brusilow, Arginine, an Indispensable Amino Acid for Patients with Inborn Errors of Urea Synthesis, J. Clin. Invest., vol. 74, Dec. 1984, 2144 2148. *
Brusilow, Arginine, an Indispensable Amino Acid for Patients with Inborn Errors of Urea Synthesis, J. Clin. Invest., vol. 74, Dec. 1984, 2144-2148.
Burns et al, Arginine: An Indispensable Amino Acid for Mature Dogs, J. Nutr. 111: 1020 1024, 1981. *
Burns et al, Arginine: An Indispensable Amino Acid for Mature Dogs, J. Nutr. 111: 1020-1024, 1981.
Carey et al, An Arginine Deficient Diet in Humans Does Not Evoke Hyperammonemia or Orotic Aciduria, American Institute of Nutrition (1987) 1734 1739. *
Carey et al, An Arginine-Deficient Diet in Humans Does Not Evoke Hyperammonemia or Orotic Aciduria, American Institute of Nutrition (1987) 1734-1739.
Chyun et al, Improvement of Nitrogen Retention by Arginine and Glycine Supplementation and Its Relation to Collagen Synthesis in Traumatixed Mature and Aged Rats, J. Nutr. 114: 1697 1704, 1984. *
Chyun et al, Improvement of Nitrogen Retention by Arginine and Glycine Supplementation and Its Relation to Collagen Synthesis in Traumatixed Mature and Aged Rats, J. Nutr. 114: 1697-1704, 1984.
Czarnecki et al, Urea Cycle Function in the Dog with Emphasis on the Role of Arginine, J. Nutr. 114: 581 590, 1984. *
Czarnecki et al, Urea Cycle Function in the Dog with Emphasis on the Role of Arginine, J. Nutr. 114: 581-590, 1984.
De Aloysio et al, The Clinical Use of Arginine Aspartate in Male Infertility, Acta Eut Fertil 1982; 13: 133 67. *
De Aloysio et al, The Clinical Use of Arginine Aspartate in Male Infertility, Acta Eut Fertil 1982; 13: 133-67.
Deshmukh et al, Arginine Requirement and Ammonia Toxicity in Ferrets, J. Nutr. 113: 1983, 1664 1667. *
Deshmukh et al, Arginine Requirement and Ammonia Toxicity in Ferrets, J. Nutr. 113: 1983, 1664-1667.
du Ruisseau et al, Studies on the Metabolism of Amino Acids and Related Compounds in Vivo, IV, Blood Ammonia and Urea Levels Following Intraperitoneal Administration of Amino Acids and . . . , Archives of Biochemistry and Biophysics 64, 355 367 (1956). *
du Ruisseau et al, Studies on the Metabolism of Amino Acids and Related Compounds in Vivo, IV, Blood Ammonia and Urea Levels Following Intraperitoneal Administration of Amino Acids and . . . , Archives of Biochemistry and Biophysics 64, 355-367 (1956).
Elsair et al, E fect of Arginine Chlorhydrate on Nitrogen Balance During the Three Days Following Routine Surgery in Man, Biomedicine, 1978, 29, 312 317. *
Elsair et al, E-fect of Arginine Chlorhydrate on Nitrogen Balance During the Three Days Following Routine Surgery in Man, Biomedicine, 1978, 29, 312-317.
Fahey et al, Effect of L Arginine on Elevated Blood Ammonia Levels in Man, American Journal of Medicine, 860 869 (1957). *
Fahey et al, Effect of L-Arginine on Elevated Blood Ammonia Levels in Man, American Journal of Medicine, 860-869 (1957).
Furst et al, Stress Induced Intracellular Glutamine Depletion, Contr. Infusion Ther. Clin. Nutr., vol. 27, (1987), 117 136. *
Furst et al, Stress-Induced Intracellular Glutamine Depletion, Contr. Infusion Ther. Clin. Nutr., vol. 27, (1987), 117-136.
Furst, "Stress Induced Intracellular Glutamine Depletion," Contr. Infusion Ther. Clin, Nutr. vol. 17, pp. 117-136 (1988).
Furst, Stress Induced Intracellular Glutamine Depletion, Contr. Infusion Ther. Clin, Nutr. vol. 17, pp. 117 136 (1988). *
Gopalakrishna et al, Effect of Growth & Differentiation on Distribution of Arginase & Arginine in Rat Tissues, Indian Journal of Biochemistry & Biophysics, vol. 16, Apr. 1979, 66 68. *
Gopalakrishna et al, Effect of Growth & Differentiation on Distribution of Arginase & Arginine in Rat Tissues, Indian Journal of Biochemistry & Biophysics, vol. 16, Apr. 1979, 66-68.
Hubl. et al. "Influence of Molecular Structure and Plasma Hydrolysis on the Metabolism of Glutamine-Containing Dipeptides in Humans," Metab 59 (1989).
Hubl. et al. Influence of Molecular Structure and Plasma Hydrolysis on the Metabolism of Glutamine Containing Dipeptides in Humans, Metab 59 (1989). *
Laidlaw et al, Newer Concepts of the Indispensable Amino Acids, Am J. Clin Nutr 1987; 46:593 605. *
Laidlaw et al, Newer Concepts of the Indispensable Amino Acids, Am J. Clin Nutr 1987; 46:593-605.
Rose, The Amino Acid Requirements of Adult Man, Nutrition Abstracts and Reviews, vol. 27, No. 3, Jul. 1957, 631 647. *
Rose, The Amino Acid Requirements of Adult Man, Nutrition Abstracts and Reviews, vol. 27, No. 3, Jul. 1957, 631-647.
Rudman et al, Hypotyrosinemia, Hypocystinemia, and Failure to Retain Nitrogen During Total Parenteral Nutrition of Cirrhotic Patients, Gastroenterology 1981:81:1025 35. *
Rudman et al, Hypotyrosinemia, Hypocystinemia, and Failure to Retain Nitrogen During Total Parenteral Nutrition of Cirrhotic Patients, Gastroenterology 1981:81:1025-35.
Stehle, P. et al., Effect of Parenteral Glutamine Peptide Supplements on Muscle Glutamine Loss and Nitrogen Balance After Major Surgery, 1 Lancet 231 (Feb. 1989). *
Steininger et al., "Infusion of Dipeptides as Nutritional Substrates for Glutamine, Tyrosine, and Branched-Chain Amino Acids in Patients with Acute Pancreatitis, "Meta. 78 (Aug. 1989).
Steininger et al., Infusion of Dipeptides as Nutritional Substrates for Glutamine, Tyrosine, and Branched Chain Amino Acids in Patients with Acute Pancreatitis, Meta. 78 (Aug. 1989). *
Takagi et al, A Novel Analgesic Dipeptide from Bovine Brain is a Possible Met Enkephalin Releaser, Nature, vol. 282, 1979, 410 412. *
Takagi et al, A Novel Analgesic Dipeptide from Bovine Brain is a Possible Met-Enkephalin Releaser, Nature, vol. 282, 1979, 410-412.
Ueda et al, A Met Enkephalin Releaser (Kyotorphin) Induced Release of Plasma Membrane bound Ca 2 From Rat Brain Synaptosomes, Brain Research 419 (1987) 197 200. *
Ueda et al, A Met-Enkephalin Releaser (Kyotorphin)-Induced Release of Plasma Membrane-bound Ca2+ From Rat Brain Synaptosomes, Brain Research 419 (1987) 197-200.
Ueda et al, Kyotorphin (Tyrosine Arginine) Synthetase in Rat Brain Synaptosomes, The Journal of Biological Chemistry, vol. 262, No. 17, 1987, 8165 8173. *
Ueda et al, Kyotorphin (Tyrosine-Arginine) Synthetase in Rat Brain Synaptosomes, The Journal of Biological Chemistry, vol. 262, No. 17, 1987, 8165-8173.

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0646375A1 (en) 1993-10-05 1995-04-05 Clintec Nutrition Company Method of regulating blood amino acid levels
US5821217A (en) * 1995-10-27 1998-10-13 Beth Israel Deaconess Medical Center, Inc. Enteral formulation: low in fat and containing protein hydrolysates
US5998363A (en) * 1995-10-27 1999-12-07 Beth Israel Deaconess Medical Center, Inc. Enteral formulation: low in fat and containing protein hydrolysates
US6743945B1 (en) * 1998-06-01 2004-06-01 Fuji Oil Co., Ltd. Carboxylic acid and amino acid or amino condensate reactants and manufacturing method therefor
US6649746B1 (en) 1999-05-07 2003-11-18 University Of Virginia Patent Foundation Biological production of stable glutamine, poly-glutamine derivatives in transgenic organisms and their use for therapeutic purposes
US20090082283A1 (en) * 1999-08-13 2009-03-26 Josef Neu Dipeptides for Prevention of Muscle Breakdown and Microbial Infection
US20040097426A1 (en) * 1999-08-13 2004-05-20 Josef Neu Dipeptides for prevention of muscle breakdown and microbial infection
US8133868B2 (en) 1999-08-13 2012-03-13 University Of Florida Research Foundation, Inc. Dipeptides for prevention of muscle breakdown and microbial infection
US7855181B2 (en) 1999-08-13 2010-12-21 University Of Florida Research Foundation, Inc. Dipeptides for prevention of muscle breakdown and microbial infection
US20060229256A1 (en) * 2003-09-26 2006-10-12 Bristol-Myers Squibb Company Enternal administration of arginine and glutamine for abnormal vascular proliferation
US20070054866A1 (en) * 2003-09-26 2007-03-08 Josef Neu Arginyl-glutamine dipeptide for treatment of pathological vascular proliferation
US7148199B2 (en) 2003-09-26 2006-12-12 University Of Florida Research Foundation, Inc. Arginyl-glutamine dipeptide for treatment of pathological vascular proliferation
US7754692B2 (en) 2003-09-26 2010-07-13 University Of Florida Research Foundation, Inc. Arginyl-glutamine dipeptide for treatment of pathological vascular proliferation
US20050089547A1 (en) * 2003-09-26 2005-04-28 Josef Neu Arginyl-glutamine dipeptide for treatment of pathological vascular proliferation
US20050070484A1 (en) * 2003-09-26 2005-03-31 Josef Neu Arginyl-glutamine dipeptide for treatment of pathological vascular proliferation
US20090270337A1 (en) * 2008-04-29 2009-10-29 Conopco, Inc., D/B/A Unilever Composition Comprising Carbohydrates and Peptides which Comprise Tryptophan
US20110166085A1 (en) * 2008-04-29 2011-07-07 Beck-Hoven Van Rudolf Composition comprising carbohydrates and peptides which comprise tryptophan
US10172375B2 (en) * 2008-04-29 2019-01-08 Dsm Ip Assets B.V. Compositions comprising carbohydrates and peptides which comprise tryptophan

Also Published As

Publication number Publication date
EP0457314A1 (en) 1991-11-21

Similar Documents

Publication Publication Date Title
US5189016A (en) Nutrient compositions containing peptides and method for administering the same
US4340592A (en) Nutrient compositions and method of administering the same
US6060446A (en) Method and composition for treating renal disease and failure
US5036052A (en) Amino acid nutrient compositions
Fairclough et al. Comparison of the absorption of two protein hydrolysates and their effects on water and electrolyte movements in the human jejunum.
AU682894B2 (en) Composition based on amino acids intended for the treatment of sepsis or of an attack bringing about an inflammatory reaction, in animals and man
US5102871A (en) Nutrient composition
EP0182356B1 (en) Nutrient compositions
JP2518692B2 (en) Muscle maintenance agent, nutrient tonic, infusion agent, nutritional supplement, fatigue recovery agent and lactic acid production regulator
US5206220A (en) Soluble and stable sources of tyrosine, cysteine and glutamine for total parenteral nutrition
PT753526E (en) A PEPTIDE INHIBITOR OF THE DIFFERENTIATION OF ADIPOCYTES FROM THE DIFFERENTIATION OF ADIPOCYTES CONTAINING THE PEPTIDE AS ACTIVE INGREDIENT
Gardner Absorption of intact peptides: studies on transport of protein digests and dipeptides across rat small intestine in vitro
Grimble Mechanisms of peptide and amino acid transport and their regulation
US5122515A (en) Nutrient composition containing dipeptides and method for administering the same
CA2134380C (en) Composition based on amino acids intended for the treatment of sepsis or of an attack bringing about an inflammatory reaction, in animals and man
JPH07330583A (en) Liquid preparation containing free glutamic acid
JPH05507472A (en) Soluble and stable source of tyrosine, cysteine and glutamine for parenteral nutrition
JPH09110686A (en) Macrophage nitrogen monoxide-producing sthenic agent
US8133868B2 (en) Dipeptides for prevention of muscle breakdown and microbial infection
HUT69785A (en) Soybean protein or hydrolylates in pharmaceutical compositions to protect bioaltive peptides from enzymatic inactivation
Elia Glutamine in parenteral nutrition
JPH07267855A (en) Glutamine producing agent
Stehle Bedarfsgerechte Bereitstellung von kurzkettigen Peptiden–eine Voraussetzung für deren Einsatz in der künstlichen Ernährung
JPH02138952A (en) Nutrient transfusion composition containing dipeptide of l-leucine
JPS6326733B2 (en)

Legal Events

Date Code Title Description
AS Assignment

Owner name: CLINTEC NUTRITION CO., DEERFIELD, IL, A CORP. OF I

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNORS:MADSEN, DAVID C.;ROWE, W. BRUCE;REEL/FRAME:005362/0725

Effective date: 19900517

FEPP Fee payment procedure

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

FPAY Fee payment

Year of fee payment: 4

AS Assignment

Owner name: BAXTER INTERNATIONAL INC., ILLINOIS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:CLINTEC NUTRITION COMPANY;REEL/FRAME:008239/0827

Effective date: 19961001

FEPP Fee payment procedure

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

Free format text: PAYER NUMBER DE-ASSIGNED (ORIGINAL EVENT CODE: RMPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

FPAY Fee payment

Year of fee payment: 8

REMI Maintenance fee reminder mailed
LAPS Lapse for failure to pay maintenance fees
STCH Information on status: patent discontinuation

Free format text: PATENT EXPIRED DUE TO NONPAYMENT OF MAINTENANCE FEES UNDER 37 CFR 1.362

FP Lapsed due to failure to pay maintenance fee

Effective date: 20050223